An important model for the understanding of the pathogenesis of autoimmune disease has been the immunological disease developed by certain inbred mice strains. To define more precisely the nature of the immunoregulatory disturbances in the murine diease, the response of New Zealand (NZ) and MRL mice to foreign and self antigens will be investigated from the viewpoint of antibody structural gene expression. The parameters to be used to assess these responses will be the pattern of restriction and the expression of common idiotypes, two important and sensitive markers from the operation of genetic control in the regulation of immune responses. As a model for the reponse to a foreign antigen, the antibody response of these mice to the protein antigen Staphylococcal nuclease will be investigated. Restriction will be determined by isoelectric focusing (IEF) and the expression of idiotypes by serological means. The anti-DNA atibody response of NZ mice and the anti-DNA and anti-Sm antibody response of MRL mice will be similarly analyzed. IEF will be used to assess the degree of restriction of autoantibody responses during the course of disease. As a source of atibodies for the production of anti-idiotypic antisera, monoclonal autoantibodies will be generated by somatic cell hybridization (hybridoma technique). The existence of commonly expressed autoantibody idiotypes will be investigated and the genetic relationship of such idiotypes to antibody structural genes determined. Structural analysis of the monoclonal antibodies will be performed to determine whether unique features of these antibodies contribute to their pathogenic role in disease. These studies thus focus on the ontogenetic role of antibody structural genes in autoimmune disease and open the possibility of the study of the regulation of autoantibody responses at the clonal or idiotype level.